DESCRIPTION (Adapted from the application): Development of antihepatitis B viral drugs (anti-HBV drugs) with enhanced potency, efficacy, bioavailability, and a broad therapeutic index is proposed. Using SCAN technology, four classes of lead molecules were identified by a high-throughput screen as small molecule ligands of virus-specific HBV epsilon RNA. All four classes of lead molecules will be subjected to structure-activity studies. In the first phase of the project, a series of small molecule analogs of the lead molecules will be synthesized with various positions substituted by electron-donating, electron withdrawing, hydrophilic, or sterically demanding groups. Other specific tasks include screening compounds for ability to bind to viral RNA and evaluating activity data to gain information about structure-activity correlations. PROPOSED COMMERCIAL APPLICATION: There are few effective antiviral therapeutic. It is estimated, for example, that over 200 million people are infected with Hepatitis B virus (HBV). This virus can cause chronic infections of the liver, leading to cirrhosis, cancer, and death. at present, there is not fully efficacious treatment for the disease. Novel small molecule therapeutics that reduce the morbidity and mortality of such infections can be identified by the proposed research program and would therefore have tremendous commercial potential.